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Ontoepigenetic profile of mouse liver reveals dynamic regulation of chromatin during development

ABSTRACT: Fetal liver is predominately a hematopoietic organ, but shortly after birth transitions into the major site for xenobiotic (drug) metabolism. The epigenetic mechanisms controlling this developmental switch remain an open door for exploration. DNA methylation (meDNA) governs many diverse cellular functions and is essential for normal development. Histone H3 lysine 4 dimethylation (H3K4me2) is detected in active gene promoters and enhancers7. Histone H3 lysine 27 trimethylation (H3K27me3) is involved in chromatin compaction around inactive genes and shows a dominant negative phenotype on gene expression. Here, we used chromatin immunoprecipitation from mouse liver to determine the contributions of meDNA, H3K4me2, and H3K27me3 on facilitating a permissive chromatin state; allowing the transition from post-hematopoiesis to drug response. BAR files that contain the intensities for all probes on the arrays. The intensities are expressed as signals estimating the fold enrichment relative to IgG input. BED files contain custom tracks that can be directly uploaded to the UCSC Genome Browser (http://genome.ucsc.edu/) and contain 3 types of tracks: Intervals, Peaks, and Active Regions. Interval Tracks show where the average signal intensity of all probes in an 800 bp sliding window are greater than the thresholds (3-fold enrichment for DNA methylation and 4-fold enrichment for histone modifications). Peak Tracks indicate the most enriched probe in a given interval. The Active Regions Track shows genomic regions containing one or more overlapping intervals. Keywords: Time Course

ORGANISM(S): Mus musculus

PROVIDER: GSE14620 | GEO | 2009/01/29

SECONDARY ACCESSION(S): PRJNA112267

REPOSITORIES: GEO

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Project description:In mature human sperm, genes of importance for embryo development (i.e. transcription factors) lack DNA methylation and bear nucleosomes with distinctive histone modifications, suggesting the specialized packaging of these developmental genes in the germline. Here, we explored the tractable zebrafish model and found conceptual conservation as well as several new features. Biochemical and mass spectrometric approaches reveal the zebrafish sperm genome packaged in nucleosomes and histone variants (and not protamine), and we find linker histones high and H4K16ac absent - key factors which may contribute to genome condensation. We examined several activating (H3K4me2/3, H3K14ac, H2AFV) and repressing (H3K27me3, H3K36me3, H3K9me3, hypoacetylation) modifications/compositions genome-wide, and find developmental genes packaged in large blocks of chromatin with coincident activating and repressing marks and DNA hypomethylation, revealing complex ‘multivalent’ chromatin. Notably, genes that acquire DNA methylation in the soma (muscle) are enriched in transcription factors for alternative cell fates. Remarkably, we find H3K36me3 located in ‘silent’ developmental gene promoters, and not present at the 3’ ends of coding regions of genes heavily transcribed during sperm maturation, suggesting different rules for H3K36me3 in the germline and soma. We also reveal the chromatin patterns of transposons, rDNA, and tRNAs. Finally, high levels of H3K4me3 and H3K14ac in sperm are correlated with genes activated in embryos prior to the mid-blastula transition (MBT), whereas multivalent genes are correlated with activation at or after MBT. Taken together, gene sets with particular functions in the embryo are packaged by distinctive types of complex and often atypical chromatin in sperm. [DNA profiling]: H3K4me3, H3K4me2, H3K14ac, H3K36me3, H3K27me3, H3K9me3, and H2AFV ChIP-chip in zebrafish sperm; DNA methylation in zebrafish sperm and muscle by MeDIP-chip. (two replicates and dye-swaps for all experiments). Antibodies: H3K4me3 (Abcam ab8580 and Active Motif 39159), H3K4me2 (Abcam ab7766), H3K14Ac (Upstate 07-353), H2AZ (Abcam ab4174), H3K27me3 (Upstate 07-449), H3K9me3 (Active Motif 39161), H3K36me3 (Abcam ab9050), 5-methylcytidine (Eurogentec BI-MECY-1000). Supplementary files: Processed data files reporting calculated enrichment log2 ratio (mean ChIP/mean Input in the log2 ratio). Note: For analysis, "mean Input" from H3K4me3-rep1 ch1, H3K4me2-rep1 ch2, and H3K36me3-rep2 ch1 for all ChIP eluates. [mRNA profiling]: Transcripts in zebrafish mature sperm using zebrafish expression microarray from Agilent. (two replicates)

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Ontoepigenetic profile of mouse liver reveals dynamic regulation of chromatin during development

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